Co-loading of bisphosphonates and antibiotics to a biomimetic hydroxyapatite coating.

We have incorporated bisphosphonates and antibiotics simultaneously into a biomimetic hydroxyapatite implant coating aiming to use the interaction between drug-molecules and hydroxyapatite to enable local release of the two different substances to obtain a dual biological effect. A sustained release over for 43 h of antibiotics (cephalothin) was achieved without negative interference from the presence of the bisphosphonate (clodronate) which, in turn, successfully bonded to the coating surface. To our knowledge, this is the first study that indicates the possibility to simultaneously incorporate both antibiotics and bisphosphonates to an implant coating, a strategy that is believed to improve implant stability and reduce implant-related infections.

Neonatal Listeria-meningitis in San Luis, Argentina: a three-case report.

Between November 1996 and December 2006, two cases of early-onset and one case of late-onset neonatal listeriosis were reported in San Luis, Argentina. This article describes clinical and laboratory findings as well as treatment and outcome for newborns treated for Listeria monocytogenes meningitis or septicaemia. In one of the newborns with early-onset listeriosis, meningitis led to important complications including hydrocephalus. The two other newborns showed complete recovery following adequate treatment. The L. monocytogenes isolates from two patients belonged to PCR group IVb (including serovar 4b strains) and to PCR group IIb (including serovar 1/2b strains) in the third patient. Listeriosis, especially the maternal-fetal presentation, is still rare in Argentina for unknown reasons. Our data can be used in the future as an epidemiological survey.

The role of antibiotics in reduction mammaplasty.

This prospective study was conducted to assess the influence of antibiotics use on surgical site infections (SSI) rates after reduction mammaplasty. Patients undergoing reduction mammaplasty were assigned to group 1 (n = 50), which received intravenous cephalotin pre- and postoperatively, besides oral cephalexin for 6 days after discharge, or to group 2 (n = 50), which received no antibiotics. Patients were followed up weekly for 30 days, regarding to SSI, by a blinded surgeon. The Centers for Disease Control and Prevention definitions and classification of SSI were adopted. There was no statistical difference between the groups in regard to age, body mass index, duration of operation, and total resection weight. SSI rates were 2% and 14% in groups 1 and 2, respectively (P = 0.03). In group 2, older patients and those with higher resection weight had significant higher SSI rates (P = 0.02 and P = 0.04, respectively). We observed that antibiotics use decreased SSI rates after reduction mammaplasty.

Multifunctional implant coatings providing possibilities for fast antibiotics loading with subsequent slow release.

The possibility to fast-load biomimetic hydroxyapatite coatings on surgical implant with the antibiotics Amoxicillin, Gentamicin sulfate, Tobramycin and Cephalothin has been investigated in order to develop a multifunctional implant device offering sustained local anti-bacterial treatment and giving the surgeon the possibility to choose which antibiotics to incorporate in the implant at the site of surgery. Physical vapor deposition was used to coat titanium surfaces with an adhesion enhancing gradient layer of titanium oxide having an amorphous oxygen poor composition at the interface and a crystalline bioactive anatase TiO(2) composition at the surface. Hydroxyapatite (HA) was biomimetically grown on the bioactive TiO(2) to serve as a combined bone in-growth promoter and drug delivery vehicle. The coating was characterized using scanning and transmission electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. The antibiotics were loaded into the HA coatings via soaking and the subsequent release and antibacterial effect were analyzed using UV spectroscopy and examination of inhibition zones in a Staphylococcus aureus containing agar. It was found that a short drug loading time of 15 min ensured antibacterial effects after 24 h for all antibiotics under study. It was further found that the release processes of Cephalothin and Amoxicillin consisted of an initial rapid drug release that varied unpredictably in amount followed by a reproducible and sustained release process with a release rate independent of the drug loading times under study. Thus, implants that have been fast-loaded with drugs could be stored for ~10 min in a simulated body fluid after loading to ensure reproducibility in the subsequent release process. Calculated release rates and measurements of drug amounts remaining in the samples after 22 h of release indicated that a therapeutically relevant dose could be achieved close to the implant surface for about 2 days. Concluding, the present study provides an outline for the development of a fast-loading slow-release surgical implant kit where the implant and the drug are separated when delivered to the surgeon, thus constituting a flexible solution for the surgeon by offering the choice of quick addition of antibiotics to the implant coating based on the patient need.

Increased incidence of postoperative infections during prophylaxis with cephalothin compared to doxycycline in intestinal surgery.

BACKGROUND: The antibiotics used for prophylaxis during surgery may influence the rate of surgical site infections. Tetracyclines are attractive having a long half-life and few side effects when used in a single dose regimen. We studied the rate of surgical site infections during changing regimens of antibiotic prophylaxis in medium and major size surgery. METHODS: Prospective registration of surgical site infection following intestinal resections and hysterectomies was performed. Possible confounding procedure and patient related factors were registered. The study included 1541 procedures and 1489 controls. The registration included time periods when the regimen was changed from doxycycline to cephalothin and back again. RESULTS: The SSI in the colorectal department increased from 19% to 30% (p=0.002) when doxycycline was substituted with cephalothin and decreased to 17% when we changed back to doxycycline (p=0.005). In the gynaecology department the surgical site infection rate did not increase significantly. Subgroup analysis showed major changes in infections in rectal resections from 20% to 35% (p=0.02) and back to 12% (p=0.003). CONCLUSION: Doxycycline combined with metronidazole, is an attractive candidate for antibiotic prophylaxis in medium and major size intestinal surgery.

Pharmacokinetics of Intraperitoneal Cefalothin and Cefazolin in Patients Being Treated for Peritoneal Dialysis-Associated Peritonitis.

UNLABELLED: ♦ BACKGROUND: The standard treatment of peritoneal dialysis (PD)-associated peritonitis (PD-peritonitis) is intraperitoneal (IP) administration of antibiotics. Only limited data on the pharmacokinetics and appropriateness of contemporary dose recommendations of IP cefalothin and cefazolin exist. The aim of this study was to describe the pharmacokinetics of IP cefalothin and cefazolin in patients treated for PD-peritonitis. ♦ METHODS: As per international guidelines, IP cefalothin or cefazolin 15 mg/kg once daily was dosed with gentamicin in a 6-hour dwell to patients with PD-peritonitis during routine care. Serial plasma and PD effluent samples were collected over the first 24 hours of therapy. Antibiotic concentrations were quantified using a validated chromatographic method with pharmacokinetic analysis performed using a non-compartmental approach. ♦ RESULTS: Nineteen patients were included (cefalothin n = 8, cefazolin n = 11). The median bioavailability for both antibiotics exceeded 92%, but other pharmacokinetic parameters varied markedly between antibiotics. Both antibiotics achieved high PD effluent concentrations throughout the antibiotic dwell. Cefazolin had a smaller volume of distribution compared with cefalothin (14 vs 40 L, p = 0.003). The median trough total plasma antibiotic concentration for cefazolin and cefalothin during the dwell differed (plasma 56 vs 13 mg/L, p < 0.0001) despite a similar concentration in PD effluent (37 vs 38 mg/L, p = 0.58). Lower antibiotic concentrations were noted during PD dwells not containing antibiotic, particularly cefalothin, which was frequently undetectable in plasma and PD effluent. The median duration that the unbound antibiotic concentration was above the minimum inhibitory concentration (MIC) was approximately 13% (plasma) and 25% (IP) for cefalothin, and 100% (plasma and IP) for cefazolin, of the dosing interval. ♦ CONCLUSIONS: When IP cefalothin or cefazolin is allowed to dwell for 6 hours, sufficient PD effluent concentrations are present for common pathogens during this time. However, with once-daily IP dosing, in contrast to cefazolin, there is a risk of subtherapeutic plasma and PD effluent cefalothin concentrations, so more frequent dosing may be required.

Empiric therapy for infections in granulocytopenic cancer patients: continuous infusion of amikacin plus cephalothin.

A combination of amikacin sulfate given by continuous infusion (800 mg/sq m/24 hr) plus cephalothin sodium (2 g every four hours) was used as initial empiric therapy for the treatment of 65 evaluable febrile (greater than 38.5 degrees C) episodes in 54 granulcoytopenic (neutrophils, less than 1,000/microliter) adult cancer patients. Carbenicillin disodium (5 g every four hours) was substituted for cephalothin in patients with Pseudomonas infections and in patients in whom the initial regimen was unsuccessful. Thirty-two of the 38(84%) identifiable infections responded to therapy, including all of the eight septicemias and eight of 11 pneumonias. Three additional infections responded to the substitution of carbenicillin for cephalothin, for a total response rate of 92% (35/38). Nephrotoxicity occurred in five patients (7.1%), most commonly in patients over 60 years of age. Ototoxicity, highly correlated with a duration of greater than 19 days and a total dosage of greater than 25 g of amikacin sulfate, occurred in four patients (5.6%). Amikacin given by continuous infusion plus cephalothin is a safe and efficacious empiric therapy for infections in granulocytopenic cancer patients.

Nephrotoxicity associated with cephalothin administration.

Variable degrees of acute renal failure developed in three patients receiving therapy with cephalothin sodium. The course and findings were consistent with acute tubular necrosis of the oliguric and nonoliguric types. One patient had protracted oliguria, a second experienced transient oliguria, and one had normal urine output. All had urinary sediment changes consistent with tubular necrosis, and the two oliguric patients had elevated urine sodium concentrations. No other causes for renal failure could be detected, and all recovered after discontinuation of cephalothin therapy, although peritoneal dialysis was required in one patient. These observations indicate that cephalothin is capable of inducing renal damage in man.

Nephrotoxicity of combined cephalothin-gentamicin regimen.

Two patients developed acute tubular necrosis, characterized clinically by acute oliguric renal failure, while they were receiving a combination of cephalothin sodium and gentamicin sulfate therapy. Patients who are given this drug regimen should be observed very carefully for early signs of nephrotoxicity. High doses of this antibiotic combination should be avoided especially in elderly patients. Patients with renal insufficiency should not be given this regimen.

Antibiotic combination-associated nephrotoxicity in granulocytopenic patients with cancer.

Antibiotic combination-associated nephrotoxicity was reviewed in 491 granulocytopenic patients with cancer and fever. Nephrotoxicity was defined as a rise in the serum creatinine level of more than 0.4 mg/dL. The different aminoglycosides, when combined with ticarcillin disodium, were found to have an equivalent nephrotoxic potential and, for the purpose of analysis, were combined and termed "aminoglycoside plus ticarcillin" (Ags + ticarcillin). Groups treated with gentamicin or amikacin plus cephalothin sodium were combined and termed "aminoglycoside plus cephalothin" (Ags + cephalothin). The rate of nephrotoxicity was statistically less for the Ags + ticarcillin group, eight (3.1%) of 262 patients, than for the Ags + cephalothin group, 23 (18.3%) of 126 patients. Age greater than 50 years was a potentiating factor for the occurrence of nephrotoxicity in the Ags + cephalothin group. We have concluded that for granulocytopenic patients with cancer and fever, the antibiotic combination of the Ags + cephalothin should not be used as empiric antibiotic therapy.

Diagnostic value of routine drain tip culture in primary joint arthroplasty.

BACKGROUND: Closed suction drainage after joint arthroplasty is common practice in many institutions. The purpose of this study was to determine the correlation between routine drain tip culture and the diagnosis of superficial or deep postoperative wound infection after primary knee and hip replacement. METHODS: Over a 12-month period, drain tips were retrieved and cultured in all patients who underwent unilateral primary total knee or hip replacement with the use of closed suction drainage. A total of 393 cultures was performed in 387 patients (145 hip replacements, 242 knee replacements). Patients were followed for an average of 8.9 months after surgery to assess for postoperative wound infection. RESULTS: Three patients had a positive drain tip culture, none of which were diagnosed with superficial or deep infection. Four patients (1%) were diagnosed with deep infection, 16 (4.1%) with superficial infection. No patient with either superficial or deep infection had a positive drain tip culture after their index procedure. The sensitivity of routine drain tip culture for the diagnosis of postoperative infection in primary joint replacement was 0% and specificity was 99.2%. CONCLUSIONS: These data do not support the practice of routine drain tip culture after primary hip or knee replacement for the diagnosis of postoperative infection.

High complication rate after syndesmotic screw removal.

PURPOSE: The aim of this study was to determine the rate of complications after routine syndesmotic screw removal. MATERIALS AND METHODS: All patients who underwent syndesmotic screw removal at our hospital between 2007 and 2012 were included in the study. Patient demographics, surgical characteristics, radiographic evaluation and complications were recorded from the patients' charts. Questionnaires were sent by postal mail to all patients, to measure patient satisfaction and pain (VAS scales). RESULTS: 161 patients were included in the trial. A wound infection was found in 8 (5%) patients. 3 were regarded as serious infections requiring hospitalisation and intravenous antibiotics, 2 of those required surgical revisions. 5 patients were treated by oral antibiotics. Staphylococcus aureus was identified as the causing organism in all (6/8) cases with a positive culture. The patients with postoperative infection reported more pain (5.3 vs. 2.3; p=0.02) and were less satisfied (4.7 vs. 7.6; p=0.014) with their ankle compared to those without infection (T-test for independent samples). CONCLUSION: There were 5% wound infections after routine syndesmotic screw removal. Routine antibiotic prophylaxis effective against S. aureus should be administered when removing syndesmotic screws. In our institution we now use one single dose Cefalotin of 2g intravenously 30-60min before screw removal.

Abiotrophia defectiva bleb-associated endophthalmitis confirmed with 16s ribosomal RNA sequencing.

One recognized complication of trabeculectomy with visually devastating potential is blebitis. We present a case of a 74-year-old woman with a culture and polymerase chain reaction-positive Abiotrophia defectiva bleb-associated endophthalmitis. Abiotrophia defectiva is a rare but possible cause of endophthalmitis secondary to blebitis and should be considered in culture-negative cases. Prompt identification, hence directed eradication, of the causative organism in such visually threatening cases may be facilitated by requesting polymerase chain reaction and 16S ribosomal RNA sequencing.

Intraleukocytic sequestration as a cause of persistent Staphylococcus aureus peritonitis in continuous ambulatory peritoneal dialysis.

Peritonitis caused by Staphylococcus aureus in four patients undergoing continuous ambulatory peritoneal dialysis failed to respond to, or relapsed immediately after cessation of, intraperitoneal antibiotic therapy with vancomycin or cephalothin and tobramycin. Sequestration of viable staphylococci within polymorphonuclear leukocytes in the peritoneal fluid was suspected for two reasons: (1) staphylococci could still be grown after treatment of the dialysate cell fraction with lysostaphin, a procedure that kills only extracellular staphylococci, and (2) diminished polymorphonuclear leukocyte bactericidal activity was demonstrated in peritoneal dialysis effluent. Addition of rifampin, which readily penetrates polymorphonuclear leukocytes, to the treatment regimen of all patients led to prompt resolution of peritonitis without relapse.

Granulocytopenia in hospitalized patients. II. A prospective comparison of two antibiotic regimens in the empiric therapy of febrile patients.

The results of empiric antibiotic therapy in 126 hospitalized patients with fever during 192 episodes of granulocytopenia were studied. Febrile granulocytopenic patients were randomly allocated to receive either carbenicillin, methicillin and gentamicin, or carbenicillin and cephalothin. The response rate for the two antibiotic regimens was similar, 49 (60 per cent) of 81 responded to the former and 42 (54 per cent) of 78 to the latter. The response rate in patients receiving other antibiotics because of specific indications or counterindications was 19 (58 per cent) of 33. Thirty-nine (35 per cent) of 110 patients who responded to initial antibiotic therapy had an increase in circulating granulocytes of one log10 or more compared to only 10 (12 per cent) of 79 nonresponders with such an increase. The mortality rate in adult patients receiving carbenicillin, methicillin and gentamicin was eight (16 per cent) of 51, compared to 18 (37 per cent) of 49 in those receiving cephalothin and carbenicillin (P less than 0.05). The significance of this difference in the initial response rate or mortality rate between patients treated with the two antibiotic regimens when only patients with documented bacterial infection were considered. Patients who responded to their initial antibiotic regimen, and patients for whose fever no explanation was found, had the best prognosis.

Infection following coronary artery surgery. Comparison of two antibiotic prophylaxis regimens.

A prospective randomized study was conducted in 200 patients undergoing coronary artery bypass surgery. All patients received intravenous (IV) cephalothin prophylaxis for 48 hours beginning with anesthetic induction. Group A (99 eligible patients) received cephalexin 500 mg po, qid for three extra days. Group B (94 eligible patients) received no oral therapy. The overall infection rate was 9.3 percent (18 patients). Six patients had multiple sites of involvement. There was no difference between group A (9.0 percent, nine patients) vs B (9.5 percent, nine patients) (p greater than 0.5). The median sternotomy infection rate, superficial or deep, was 2.6% (five patients). The surgical wound infection rate was 4.7 percent (nine patients). The overall infection rate compares favorably with that of high risk groups for clean surgical procedures defined in SENIC study. There was no advantage to prolonged oral cephalexin prophylaxis following coronary artery bypass (CAB) surgery.

Cephalothin prophylaxis assay during cardiopulmonary bypass.

Efficient use of prophylactic antibiotics in surgery demands their presence in adequate serum concentration at the time of maximal potential contamination. This cover should extend from the moment of incision until at least the time of removal of large tubes and intravenous connulas. Critical cardiac contamination may occur during the bypass procedure while the operation within the cardiac chambers is being done. This is a special danger in valve replacement with prostheses. The antibiotic regimen of the Cardiothoracic Unit was studied in 12 consecutive patients and was generally found to provide adequate antibiotic coverage throughout the surgical procedure, including the bypass procedure. In all patients, a reinforcing cephalothin dose on completion of bypass ensured adequate circulating cephalothin levels for the completion of surgery. Clearance of the cephalothin from the blood of patients was found to decrease markedly during cardiopulmonary bypass.

Cephalothin prophylaxis in cardiac valve surgery. A prospective, double-blind comparison of two-day and six-day regimens.

A prospective, double-blind study comparing a 6 day with a 2 day regimen of cephalothin prophylaxis was conducted among 200 patients undergoing prosthetic valve replacement. No cases of endocarditis occurred during the 2 month follow-up. Sternal wound infection developed in 2.8 per cent of the 6 day group and 2.1 per cent of the 2 day group. Pneumonia developed in 8.5 per cent of the 6 day and 5.3 per cent of the 2 day group; most of the bacteria isolated were susceptible to cephalothin. Urinary tract infection developed more frequently in the 2 day group (17.0 versus 8.5 per cent), particularly during the first 6 postoperative days. Three of 11 patients with no detectable cephalothin in their sera at the close of operation developed staphylococcal wound infections, compared with 2 of 175 patients whose sera contained cephalothin at the close of surgery (p = 0.002, Fisher's exact test). A short course of prophylactic antibiotics is prudent, but there is no justification for prolonging their administration.

Comparative study of prophylactic antibiotics in cardiac surgery. Clindamycin versus cephalothin.

A randomized, prospective study of the relative effectiveness of clindamycin versus cephalothin was performed in 263 adult patients having cardiac surgery from September, 1977, to August, 1978. There were no statistically significant differences in frequency of postoperative infections in these two antibiotic groups. Wound infection developed in 6.5 percent of the cephalothin group and 3.2 percent of the clindamycin group. Urinary tract infection developed in 5.6 percent of the clindamycin group and 2.1 percent of the cephalothin group. Four bacteremic episodes occurred in the clindamycin-treated patients, and one episode of bacteremia occurred in a cephalothin-treated patient. No cases of endocarditis occurred during the study. Clindamycin deserved consideration as an alternative prophylactic agent to cephalothin for cardiac surgery.

Antibiotic prophylaxis for coronary bypass grafting. Comparison of a five-day and a two-day course.

A trial was conducted to compare the effectiveness of a 2 day and a 5 day course of antibiotic prophylaxis after coronary bypass grafting. One hundred sixty patients were randomized to one of the two courses. The 2 day course comprised 48 hours of intramuscular kanamycin and intravenous cephalothin. The 5 day course comprised 48 hours of intramuscular kanamycin and intravenous cephalothin followed by 3 days of oral cephalexin. After the 2 day course, there were two wound infections and two respiratory tract infections in 79 patients (5.1%), and after the 5 day course, one wound infection and two respiratory tract infections in 81 patients (3.7%). Subsequently, in 171 patients undergoing coronary bypass grafting and given the 2 day course, the infection rate was 3.5%. There was no significant difference in infection rates among the three groups (p greater than 0.05). We conclude that no more than 2 days of antibiotic prophylaxis are necessary for patients undergoing coronary bypass grafting.